Structure of PDB 5wg6 Chain A Binding Site BS08

Receptor Information
>5wg6 Chain A (length=517) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RFRRADEVKSMFSSNRQKILERTEILNQEWKQRRIQPVHILTSVRECSVT
SDLDFPTQVIPLKTLNAVASVPIMYSWSPLQQNFMVEDTPNIDGPNAKSV
QREQSLHSFHTLFCRRCFKYDCFLHPFHATPNTYKRWSGAEASMFRVLIG
TYYDNFCAIARLIGTKTCRQVYEFRVKVYNYQPCDHPRQPCDSSCPCVIA
QNFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPDLCLTCG
AADHRDSKNVSCKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFIS
EYCGEIISQDEADRRGKVYDKYMCSFLFNLNNDFVVDATRKGNKIRFANH
SVNPNCYAKVMMVNGDHRIGIFAKRAIQTGEELFFDYRYSQNRLYFHSDT
CLPLRPQEMEVDSEDEKDPEWLREKTITQIEEFSDVNEGEKEVMKLWNLH
VMKHGFIADNQMNHACMLFVENYGQKIIKKNLCRNFMLHLVSMHDFNLIS
IMSIDKAVTKLREMQQK
Ligand information
Ligand IDA9G
InChIInChI=1S/C31H38N6O2/c1-6-22(5)37-18-20(3)29-25(30(38)34-17-26-19(2)13-21(4)35-31(26)39)14-24(15-27(29)37)23-7-8-28(33-16-23)36-11-9-32-10-12-36/h7-8,13-16,18,22,32H,6,9-12,17H2,1-5H3,(H,34,38)(H,35,39)/t22-/m0/s1
InChIKeyFKSFKBQGSFSOSM-QFIPXVFZSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6CC[C@H](C)n1cc(c2c1cc(cc2C(=O)NCC3=C(C=C(NC3=O)C)C)c4ccc(nc4)N5CCNCC5)C
ACDLabs 12.01c3c(c1cnc(cc1)N2CCNCC2)cc5c(c3C(NCC=4C(=O)NC(C)=CC=4C)=O)c(cn5C(CC)C)C
OpenEye OEToolkits 2.0.6CCC(C)n1cc(c2c1cc(cc2C(=O)NCC3=C(C=C(NC3=O)C)C)c4ccc(nc4)N5CCNCC5)C
CACTVS 3.385CC[CH](C)n1cc(C)c2c1cc(cc2C(=O)NCC3=C(C)C=C(C)NC3=O)c4ccc(nc4)N5CCNCC5
CACTVS 3.385CC[C@H](C)n1cc(C)c2c1cc(cc2C(=O)NCC3=C(C)C=C(C)NC3=O)c4ccc(nc4)N5CCNCC5
FormulaC31 H38 N6 O2
Name1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3-methyl-6-[6-(piperazin-1-yl)pyridin-3-yl]-1H-indole-4-carboxamide
ChEMBLCHEMBL3287735
DrugBank
ZINCZINC000072318146
PDB chain5wg6 Chain A Residue 9009 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB5wg6 An Evolutionarily Conserved Structural Platform for PRC2 Inhibition by a Class of Ezh2 Inhibitors.
Resolution3.901 Å
Binding residue
(original residue number in PDB)		I109 W624 Y658 Y661 F665 T678 R685 F686 N688
Binding residue
(residue number reindexed from 1)		I73 W285 Y319 Y322 F326 T339 R346 F347 N349
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=4.54,IC50=28.6uM
Enzymatic activity
Enzyme Commision number 2.1.1.356: [histone H3]-lysine(27) N-trimethyltransferase.
2.1.1.43: Transferred entry: 2.1.1.354.
Gene Ontology
Molecular Function
GO:0000976 transcription cis-regulatory region binding
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding
GO:0001222 transcription corepressor binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003714 transcription corepressor activity
GO:0003723 RNA binding
GO:0005515 protein binding
GO:0008168 methyltransferase activity
GO:0016279 protein-lysine N-methyltransferase activity
GO:0031490 chromatin DNA binding
GO:0031491 nucleosome binding
GO:0042054 histone methyltransferase activity
GO:0042393 histone binding
GO:0043021 ribonucleoprotein complex binding
GO:0043565 sequence-specific DNA binding
GO:0046976 histone H3K27 methyltransferase activity
GO:0070878 primary miRNA binding
GO:0106222 lncRNA binding
GO:0140938 histone H3 methyltransferase activity
GO:0140951 histone H3K27 trimethyltransferase activity
GO:1990841 promoter-specific chromatin binding
Biological Process
GO:0000082 G1/S transition of mitotic cell cycle
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0006325 chromatin organization
GO:0006338 chromatin remodeling
GO:0006346 DNA methylation-dependent heterochromatin formation
GO:0006355 regulation of DNA-templated transcription
GO:0006357 regulation of transcription by RNA polymerase II
GO:0008284 positive regulation of cell population proliferation
GO:0009913 epidermal cell differentiation
GO:0010468 regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0014013 regulation of gliogenesis
GO:0014834 skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration
GO:0014898 cardiac muscle hypertrophy in response to stress
GO:0021695 cerebellar cortex development
GO:0021766 hippocampus development
GO:0030097 hemopoiesis
GO:0030183 B cell differentiation
GO:0030216 keratinocyte differentiation
GO:0030335 positive regulation of cell migration
GO:0031048 regulatory ncRNA-mediated heterochromatin formation
GO:0031507 heterochromatin formation
GO:0031509 subtelomeric heterochromatin formation
GO:0032259 methylation
GO:0032355 response to estradiol
GO:0034244 negative regulation of transcription elongation by RNA polymerase II
GO:0035984 cellular response to trichostatin A
GO:0036211 protein modification process
GO:0036333 hepatocyte homeostasis
GO:0042127 regulation of cell population proliferation
GO:0042752 regulation of circadian rhythm
GO:0043406 positive regulation of MAP kinase activity
GO:0043547 positive regulation of GTPase activity
GO:0045605 negative regulation of epidermal cell differentiation
GO:0045617 negative regulation of keratinocyte differentiation
GO:0045814 negative regulation of gene expression, epigenetic
GO:0045892 negative regulation of DNA-templated transcription
GO:0048387 negative regulation of retinoic acid receptor signaling pathway
GO:0048511 rhythmic process
GO:0048863 stem cell differentiation
GO:0050767 regulation of neurogenesis
GO:0051154 negative regulation of striated muscle cell differentiation
GO:0051932 synaptic transmission, GABAergic
GO:0070301 cellular response to hydrogen peroxide
GO:0070314 G1 to G0 transition
GO:0071168 protein localization to chromatin
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090183 regulation of kidney development
GO:0097421 liver regeneration
GO:0140718 facultative heterochromatin formation
GO:1900006 positive regulation of dendrite development
GO:1900016 negative regulation of cytokine production involved in inflammatory response
GO:1902808 positive regulation of cell cycle G1/S phase transition
GO:1904772 response to tetrachloromethane
GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
GO:2000737 negative regulation of stem cell differentiation
Cellular Component
GO:0000781 chromosome, telomeric region
GO:0000785 chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005677 chromatin silencing complex
GO:0005694 chromosome
GO:0005721 pericentric heterochromatin
GO:0035098 ESC/E(Z) complex
GO:0045120 pronucleus
GO:0045202 synapse

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5wg6, PDBe:5wg6, PDBj:5wg6
PDBsum5wg6
PubMed29904056
UniProtQ15022|SUZ12_HUMAN Polycomb protein SUZ12 (Gene Name=SUZ12);
Q15910|EZH2_HUMAN Histone-lysine N-methyltransferase EZH2 (Gene Name=EZH2)

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